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Immunological Correlates of Response to Immune Checkpoint Inhibitors in Metastatic Urothelial Carcinoma
Background The identification of prognostic and/or predictive biomarkers for response to immune checkpoint inhibitors (ICI) could help guide treatment decisions. Objective We assessed changes in programmed cell death-1 (PD1)/PD1 ligand (PDL1) expression in key immunomodulatory cell subsets (myeloid-...
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Published in: | Targeted oncology 2018-10, Vol.13 (5), p.599-609 |
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Main Authors: | , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Background
The identification of prognostic and/or predictive biomarkers for response to immune checkpoint inhibitors (ICI) could help guide treatment decisions.
Objective
We assessed changes in programmed cell death-1 (PD1)/PD1 ligand (PDL1) expression in key immunomodulatory cell subsets (myeloid-derived suppressor cells [MDSC]; cytotoxic T lymphocytes [CTL]) following ICI therapy and investigated whether these changes correlated with outcomes in patients with metastatic urothelial carcinoma (mUC).
Patients and Methods
Serial peripheral blood samples were collected from ICI-treated mUC patients. Flow cytometry was used to quantify PD1/PDL1 expression on MDSC (CD33
+
HLADR
−
) and CTL (CD8
+
CD4
−
) from peripheral blood mononuclear cells. MDSC were grouped into monocytic (M)-MDSC (CD14
+
CD15
−
), polymorphonuclear (PMN)-MDSC (CD14
−
CD15
+
), and immature (I)-MDSC (CD14
−
CD15
−
). Mixed-model regression and Wilcoxon signed-rank or rank-sum tests were performed to assess post-ICI changes in immune biomarker expression and identify correlations between PD1/PDL1 expression and objective response to ICI.
Results
Of 41 ICI-treated patients, 26 received anti-PDL1 (23 atezolizumab/3 avelumab) and 15 received anti-PD1 (pembrolizumab) therapy. Based on available data, 27.5% had prior intravesical Bacillus Calmette–Guérin therapy, 42% had prior neoadjuvant chemotherapy, and 70% had prior cystectomy or nephroureterectomy. Successive doses of anti-PDL1 correlated with decreased percentage of PDL1
+
(%PDL1
+
) M-MDSC, while doses of anti-PD1 correlated with decreased %PD1
+
M- and I-MDSC. Although pre-treatment %PD1
+
CTL did not predict response, a greater %PD1
+
CTL within 9 weeks after ICI initiation correlated with objective response.
Conclusions
Treatment with ICI correlated with distinct changes in PD1/PDL1-expressing peripheral immune cell subsets, which may predict objective response to ICI. Further studies are required to validate immune molecular expression as a prognostic and/or predictive biomarker for long-term outcomes in mUC. |
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ISSN: | 1776-2596 1776-260X |
DOI: | 10.1007/s11523-018-0595-9 |